Intracellular second messenger cAMP is involved in relaxation of airway smooth muscles and regulation of the functions of inflammatory cells. cAMP is broken down by phosphodiesterase (PDE) and becomes inactive 5'-AMP. It is considered that an increase in concentration of cAMP due to suppression of cAMP metabolism by PDE would give bronchodilating and anti-inflammatory actions and would exhibit a therapeutic effect on inflammatory diseases such as asthma [Eur. Respir. J., 7, 579 (1994)]. Up to now, PDE has been classified into five isozymes (i.e., types I to V PDE). Their distributions differ among tissues [Trends Pharm., Sci., 12, 19 (1991)]. This suggests a possibility that selective inhibitors of PDE isozymes would result in tissue specific increase of intracellular cAMP concentration.
It is reported that a selective inhibitor of type IV PDE isozyme suppresses inflammatory cells functions [Thorax, 46, 512 (1991)] and is useful for inflammatory diseases such as asthma [J. Pharmacol. Exp. Ther., 266, 306 (1993)] and dermatitis [Br. J. Pharmacol., 112, 332 (1994)] and autoimmune diseases such as multiple sclerosis [Nature Medicine, 1, 244 (1994)] and rheumatoid arthritis [Clin. Exp. Immunol., 100, 126 (1995)].
In addition, it is thought that cardiovascular side effect caused by non-selective PDE inhibitors such as theophylline could be reduced by using selective type IV PDE inhibitor. Rolipram having the following formula (Japanese Unexamined Patent Publication (Kokai) No. 50-157360) is known as a compound having a specific inhibitory activity against type IV PDE. ##STR2##
Although other compounds having a specific inhibitory activity against type IV PDE are known (Japanese Unexamined Patent Publication (Kokai) No. 62-281864, U.S. Pat. No. 5,128,358, WO 94/10118, WO 94/12461, Japanese Unexamined Patent Publication (Kokai) No. 5-117239, Japanese Unexamined Patent Publication (Kokai) No. 7-101861, WO 95/03794, WO 95/08534, etc.), they have not been clinically applied up to now. Thus, more useful compounds are desired to be. Further, Japanese Unexamined Patent Publication (Kokai) No. 64-6262 discloses a compound having the following formula (II) ##STR3##
wherein W is optionally substituted phenyl group, and RI is secondary or tertiary C.sub.3 to C.sub.6 alkyl group as a synthetic intermediate of a compound having the activity of increasing the weight gain of livestock and/or improving feed utilization efficiency. Japanese Unexamined Patent Publication (Kokai) No. 59-116288 describes a compound having the following formula (III): ##STR4##
wherein R and R.sub.1 may be the same or different and represent a hydrogen atom, a C.sub.1 to C.sub.18 alkyl group or a phenyl group, which groups may be substituted, R.sub.2 represents a hydrogen atom, a C.sub.1 to C.sub.6 alkyl group, a C.sub.8 to C.sub.18 arylalkyl group which may be substituted with any number up to five of fluorine atoms, chlorine atoms, or bromine atoms, etc.
as a synthetic intermediate of a compound having a lipoxygenase inhibitory activity. U.S. Pat. No. 3,308,121 describes a compound having the following formula (IV): ##STR5##
wherein R.sub.3 represents a hydrogen atom or a lower hydroxyalkyl group, R.sub.4 represents a hydrogen atom, a lower alkyl group, an acyl group, etc., R.sub.5 and R.sub.6 independently represent a hydrogen atom, a lower alkyl group or an aryl group, Ar represents a phenyl group and a substituted phenyl group substituted with a halogen atom, a hydroxy group, a lower alkoxy group, a benzyloxy or a halogenated lower alkyl group, and X indicates an oxygen atom or a sulfur atom,
as a muscle relaxant and tranquillizer.